POS0618 CLASSICAL PATHWAY OF THE COMPLEMENT SYSTEM RELATES TO SUBCLINICAL ATHEROMATOSIS IN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: M. Garcia Gonzalez, J. C. Quevedo-Abeledo, I. Ferraz-Amaro
Journal: Annals of the Rheumatic Diseases (2022)

Background Rheumatoid arthritis (RA) is associated with arteriosclerosis. The inflammation present in the disease is responsible for this cardiovascular (CV) comorbidity. The complement system (C) is an essential component of the immune response that has the function of enhancing the inflammatory response. C has been implicated in the etiopathogenic mechanisms of CV disease and RA. Objectives Our objective was first to determine the serum levels of different molecules of the classical C pathway to fully characterize it in patients with RA. In a second step, we analyzed the relationship of this classic C pathway with the CV comorbidity and subclinical atheromatosis of a large series of patients with RA. Methods Cross-sectional study of 430 patients with RA. Clinical and analytical information related to CV disease was collected: presence of CV risk factors, lipid profile, indices of insulin resistance (HOmeostatic Model Assessment - HOMA2-), as well as measurement of intima media thickness and detection of carotid plaque by ultrasound. Plasma levels of C3, C4, C1-inhibitor and CH50 assay were assessed. Multivariable linear and logistic regressions was performed to study the relation of these molecules of the classical C pathway to the characteristics of the disease, CV comorbidity and subclinical atheromatosis. Results C3, C4 y C1-inh were highly and positively correlated with each other (p&lt;0.001). However, although CH50 functional test was strongly interrelated to C3 and C1-inh, correlation index to C4 was found to be weak (Pearson r 0.126, p=0.049). In the univariable analysis the four parameters (C3, C4, C1-inh and CH50) were, in general, associated with classical CV risk factors. In this sense, C3 and C4, but not C1-inh and CH50, were positively associated with body mass index, and abdominal circumference. Similarly, hypertension and the use of statins were associated with significant higher serum levels of C3, C4 and C1-inh, but not CH50; and the presence of dyslipidemia was related to higher circulating C3 and CH50. Likewise, in non-diabetic RA patients, C3, but not the other parameters, were significantly related to higher HOMA2-insulin resistance, and beta cell function indices after adjustment for covariates. Besides, after fully multivariable analysis, disease activity and acute phase reactants were positively related with significant higher serum levels of the three C component and the CH50 assay. Similarly, the use of NSAIDs, anti-TNF therapies, and tocilizumab, but not other therapies, were related to lower circulating C3, C4 and C1-inh, but not CH50. After adjustment for covariables that included traditional CV risk factors, CH50, but not the other C components, was positively associated with higher carotid intima-media thickness (beta coef. 1 [CI95% 1-2] microns, p&lt;0.001). Similarly, C3 (OR 1.01 [CI95% 1.00-1.02], p&lt;0.021), C1-inh (OR 1.05 [CI95% 1.01-1.08], p&lt;0.007), and CH50 (OR 1.02 [CI95% 0.99-1.03], p=0.067) were associated with the presence of carotid plaque. Conclusion Classical pathway of the C system is activated in patients with RA. Its serum components and functional assay are associated with disease activity and several disease-related data. Moreover, C’s classical pathway is related to traditional CV risk factors and to the subclinical carotid atherosclerosis present in the disease. Our findings highlight the role of C system in RA, and propose its therapeutical inhibition as a tool to control both the disease activity and the CV comorbidity that accompanies the disease. Disclosure of Interests MARIA GARCIA GONZALEZ: None declared, Juan Carlos Quevedo-Abeledo: None declared, Iván Ferraz-Amaro Speakers bureau: Dr. Iván Ferraz-Amaro would like to acknowledge that he has received grants/research supports from Abbott, MSD, Jansen and Roche, as well as consultation fees from company sponsored speakers’ bureaus associated with Abbott, Pfizer, Roche, Sanofi, Celgene, Grant/research support from: Dr. Iván Ferraz-Amaro would like to acknowledge that he has received grants/research supports from Abbott, MSD, Jansen and Roche, as well as consultation fees from company sponsored speakers’ bureaus associated with Abbott, Pfizer, Roche, Sanofi, Celgene